PROJECT SUMMARY/ABSTRACT The goal of this Midcareer Investigator Award in Patient Oriented Research is to provide key mentorship, resources and protected time to strengthen Dr. Catherine Hough's success in mentoring students, post- doctoral fellows and junior faculty in the science of patient-centered outcomes after the acute illness and injury, with a focus on the acute respiratory distress syndrome and critical illness. Although hospital mortality after critical illness has improved significantly over the past decades, there is increasing recognition that recovery is incomplete, with a substantial burden of disability and impairments in function and health-related quality of life among ICU survivors. Interventions to improve these patient-centered outcomes have been largely unsuccessful, and understanding of the mechanisms of post-ICU impairments remains quite limited. Recently, there has been increased recognition that pre-morbid health and disability are significant contributors to post- ICU impairment and to the heterogeneous trajectories of recovery, but research and clinical practice have been stalled by the difficulty of assessing pre-morbid factors at the time of ICU admission. Moving the field forward will require innovative approaches to phenotyping patients using clinical data and techniques from clinical epidemiology and health services research. Dr. Hough is an ideal candidate to provide mentorship in this area. She is a mid-career investigator with expertise in observational and interventional studies of outcomes after ARDS and critical illness, and she has a strong and growing track record in successful mentorship in patient- oriented research as well as a strong existing research program. In this award, Dr. Hough will enhance and advance her career in three ways. She will participate in structured activities to develop her mentoring skills, including one-on-one sessions with Dr. Randy Curtis, local in-person workshops and national web-based programs. She will gain content knowledge on muscle biology, use of computed tomography images in assessing muscle mass and quality. Additionally, she will work with methods experts to learn to incorporate clinical and administrative data of co-morbidity and health-care utilization into developing phenotypes of premorbid disease that predict disability and recovery. The scientific goal of this project is to investigate the relationship between premorbid muscle mass and quality, assessed via analysis of existing computed tomography scans, and short and long-term outcomes after critical illness, including muscle strength, function and disability. This project will leverage two ongoing R01-funded prospective cohorts for which Dr. Hough is a PI which contain detailed assessment of co-morbidities and pre-morbid health care utilization, prospective assessments of muscle strength and function during and after critical illness, and will create new opportunities for mentored research. Dr. Hough's career development and scientific aims will provide an outstanding environment for training of patient-oriented researchers focused on improving outcomes after critical illness.